Neutrophil-Derived Proteins: Selling Cytokines by the Pound

Department of Pathology, Faculty of Medicine, University of Verona, Italy.
Advances in Immunology (Impact Factor: 5.96). 02/1999; 73:369-509. DOI: 10.1016/S0065-2776(08)60791-9
Source: PubMed
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    • "Mediators of chronic inflammation, both cellular (e.g., leukocytes and platelets) and biochemical (cytokines and chemokines), are potent stimuli for angiogenesis [40], [41]. The immune pathogenesis of IBD is associated with an increase of chronic inflammatory mediators, including infiltration of neutrophils, activation of macrophages, and unregulated production of proinflammatory molecules in the colon. "
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    ABSTRACT: Allyl isothiocyanate (AITC) is a phytochemical found in cruciferous vegetables that has known chemopreventive and chemotherapeutic activities. Thus far, the antiangiogenic activity of AITC has not been reported in in vivo studies. Herein, we investigated the effect of AITC on angiogenesis and inflammation in a mouse model of colitis. Experimental colitis was induced in mice by administering 3% dextran sulfate sodium via drinking water. To monitor the activity of AITC in this model, we measured body weight, disease activity indices, histopathological scores, microvascular density, myeloperoxidase activity, F4/80 staining, inducible nitric oxide synthase (iNOS) expression, cyclooxygenase-2 (COX-2) expression, and vascular endothelial growth factor (VEGF)-A/VEGF receptor 2 (VEGFR2) expression in the mice. We found that AITC-treated mice showed less weight loss, fewer clinical signs of colitis, and longer colons than vehicle-treated mice. AITC treatment also significantly lessened the disruption of colonic architecture that is normally associated with colitis and repressed the microvascularization response. Further, AITC treatment reduced both leukocyte recruitment and macrophage infiltration into the inflamed colon, and the mechanism these activities involved repressing iNOS and COX-2 expression. Finally, AITC attenuated the expression of VEGF-A and VEGFR2. Thus, AITC may have potential application in treating conditions marked by inflammatory-driven angiogenesis and mucosal inflammation.
    PLoS ONE 07/2014; 9(7):e102975. DOI:10.1371/journal.pone.0102975 · 3.23 Impact Factor
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    • "Neutrophil-derived MMP9 has been found to be important in models of skin and rip-Tag pancreatic cancers (1) where they sustain tumor angiogenesis. TNFα, a cytokine released into the TUMIC and linked to tumor progression (65), induces neutrophil degranulation and VEGF release (66) and CXCL8, CXCL1 production (67), thus favoring angiogenesis. "
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    ABSTRACT: It is widely accepted that the tumor microenvironment (TUMIC) plays a major role in cancer and is indispensable for tumor progression. The TUMIC involves many "players" going well beyond the malignant-transformed cells, including stromal, immune, and endothelial cells (ECs). The non-malignant cells can acquire tumor-promoting functions during carcinogenesis. In particular, these cells can "orchestrate" the "symphony" of the angiogenic switch, permitting the creation of new blood vessels that allows rapid expansion and progression toward malignancy. Considerable attention within the context of tumor angiogenesis should focus not only on the ECs, representing a fundamental unit, but also on immune cells and on the inflammatory tumor infiltrate. Immune cells infiltrating tumors typically show a tumor-induced polarization associated with attenuation of anti-tumor functions and generation of pro-tumor activities, among these angiogenesis. Here, we propose a scenario suggesting that the angiogenic switch is an immune switch arising from the pro-angiogenic polarization of immune cells. This view links immunity, inflammation, and angiogenesis to tumor progression. Here, we review the data in the literature and seek to identify the "conductors" of this "orchestra." We also suggest that interrupting the immune → inflammation → angiogenesis → tumor progression process can delay or prevent tumor insurgence and malignant disease.
    Frontiers in Oncology 07/2014; 4:131. DOI:10.3389/fonc.2014.00131
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    • "However, whereas hypoxia induces the upregulation of VEGF expression in TAMs, neutrophil VEGF-release remains unaffected by the oxygen levels (82). In contrast, exposure to TNFα triggers the release of VEGF directly from neutrophils (83) and furthermore, TNFα induces the production of the angiogenic chemokines CXCL8 and CXCL1 (84, 85). Finally, CXCL8 can trigger neutrophil MMP-9 release, which in turn generates a highly active form of CXCL8 by means of protein cleavage (86), thereby creating feed forward loop involving release of angiogenic cytokines and additional neutrophil recruitment. "
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    ABSTRACT: Angiogenesis, the formation of new blood vessels, as well as inflammation with massive infiltration of leukocytes are hallmarks of various tumor entities. Various epidemiological, clinical, and experimental studies have not only demonstrated a link between chronic inflammation and cancer onset but also shown that immune cells from the bone marrow such as tumor-infiltrating macrophages significantly influence tumor progression. Tumor angiogenesis is critical for tumor development as tumors have to establish a blood supply in order to progress. Although tumor cells were first believed to fuel tumor angiogenesis, numerous studies have shown that the tumor microenvironment and infiltrating immune cell subsets are important for regulating the process of tumor angiogenesis. These infiltrates involve the adaptive immune system including several types of lymphocytes as well as cells of the innate immunity such as macrophages, neutrophils, eosinophils, mast cells, dendritic cells, and natural killer cells. Besides their known immune function, these cells are now recognized for their crucial role in regulating the formation and the remodeling of blood vessels in the tumor. In this review, we will discuss for each cell type the mechanisms that regulate the vascular phenotype and its impact on tumor growth and metastasis.
    Frontiers in Oncology 04/2014; 4:69. DOI:10.3389/fonc.2014.00069
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